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RESPIRATORY · FOUNDATIONS
How the lung is developed in utero, how breathing begins at delivery, and the physiology that sits underneath neonatal respiratory disease.
EMBRYOLOGY
Lung development runs through five overlapping stages, from a small bud off the foregut to alveoli that keep multiplying for years after birth. Where development stops largely determines what is survivable - and which problems appear.
Embryonic
Weeks 4-7The lung begins as a respiratory diverticulum (lung bud) off the ventral foregut. The trachea separates from the oesophagus and divides into the main and lobar bronchi, laying down the proximal airway template.
Clinical link: faulty tracheo-oesophageal separation underlies oesophageal atresia and tracheo-oesophageal fistula.Pseudoglandular
Weeks 5-17Repeated branching (branching morphogenesis) builds the conducting airways down to the terminal bronchioles. The tissue looks gland-like and no gas exchange is possible yet. The diaphragm also completes during this window.
Clinical link: failure of the pleuroperitoneal canal to close causes congenital diaphragmatic hernia; abnormal airway budding gives CPAM and sequestration.Canalicular
Weeks 16-26The respiratory portion forms - respiratory bronchioles and early acini. Capillaries proliferate against a thinning epithelium, and type I (gas exchange) and type II (surfactant) pneumocytes differentiate. Surfactant production begins around 24 weeks - close to the threshold of viability.
Clinical link: the lower the gestation, the thicker the air-blood barrier and the less surfactant - the core problem in extreme prematurity.Saccular
Weeks 24-38Terminal saccules expand the gas-exchange surface, the interstitium thins further, and surfactant rises towards maturity (around 35 weeks). Gas exchange is feasible, though reserve is limited at the earlier end.
Clinical link: surfactant deficiency through this period is the basis of respiratory distress syndrome.Alveolar
Week 36 - childhoodTrue alveoli form by secondary septation. Only a fraction of the adult alveolar number is present at term; most alveoli form over the first years of life. This is why early lung injury has such lasting effects.
Clinical link: injury during active alveolarisation (ventilation, oxygen, inflammation) drives bronchopulmonary dysplasia.KEY MOLECULES & FLUID
Made by type II pneumocytes, surfactant is mostly phospholipid (predominantly DPPC / lecithin) plus surfactant proteins. It lowers alveolar surface tension so alveoli don't collapse at end-expiration.
By Laplace's law (P = 2T/r), a smaller alveolar radius means a higher collapsing pressure - surfactant offsets this and raises compliance. Maturity is signalled by a lecithin:sphingomyelin (L/S) ratio ≥2, and antenatal corticosteroids accelerate its production.
The fetal lung actively secretes fluid that keeps it distended - essential for normal growth. Too little distension (oligohydramnios, large CDH) causes pulmonary hypoplasia.
Near term, labour catecholamines switch the epithelium from chloride secretion to sodium absorption (ENaC), and the lungs clear fluid. Delayed clearance - typically after caesarean without labour - produces transient tachypnoea of the newborn.
EXTRAUTERINE TRANSITION
The fetal lung has never done gas exchange. At birth the infant must turn a fluid-filled, high-resistance organ into an air-filled one that can oxygenate and ventilate - within minutes. Four physiological events have to occur, and respiratory distress follows when any one of them fails.
Step 1
Clear the fluidThe fetal lung actively secretes chloride-rich fluid (~20-30 mL/kg by term) that is needed for lung growth and expansion. In labour, the catecholamine and cortisol surge switches the epithelium from chloride secretion to sodium (and water) absorption; the first large breaths then force remaining fluid into the interstitium, where capillaries and lymphatics clear it.
Clinical link: incomplete clearance - caesarean without labour, maternal diabetes, prematurity - causes transient tachypnoea of the newborn.Step 2
Establish FRCThe first breath is one of the hardest efforts of life - peak pressures of 40-80 cmH₂O overcome fluid, surface tension and a compliant chest wall. Once alveoli open, surfactant lowers surface tension and later breaths are easier. Newborns defend their functional residual capacity with expiratory braking (partial glottic closure - i.e. grunting, which generates PEEP) and periodic sigh breaths - especially important in preterms.
Clinical link: too little surfactant to hold alveoli open at end-expiration → respiratory distress syndrome.Step 3
Open the circulationIn utero, pulmonary vascular resistance is high (fluid-filled alveoli, low alveolar oxygen, vasoconstrictor mediators) and most right-ventricular output bypasses the lungs through the duct. At birth, lung inflation stretches the pulmonary vessels, the rise in PaO₂ is a potent vasodilator, and endothelial nitric oxide and prostacyclin open the circulation - pulmonary blood flow surges. Rising left atrial pressure then closes the foramen ovale, and the duct constricts over the next 24-72 hours.
Clinical link: when PVR fails to fall (meconium aspiration, sepsis, pneumonia, pulmonary hypoplasia, CDH) → persistent pulmonary hypertension.Step 4
Keep breathingCentral chemoreceptors in the medulla respond to CO₂ and H⁺ (CO₂ crossing into CSF) - not to oxygen. Peripheral chemoreceptors in the carotid and aortic bodies give the dominant response to hypoxaemia (and also to hypercapnia and acidosis). Preterm control is immature: reduced CO₂ sensitivity, immature peripheral receptors and less stable rhythm generation.
Clinical link: immature respiratory control → apnoea of prematurity (responsive to caffeine).If you remember only five things
SUPPORTING CONCEPTS
Compliance (volume change per unit pressure) is low in the surfactant-deficient and preterm lung; resistance is set by the airways. Their product is the time constant - short in RDS, so alveoli fill and empty quickly.
High surface tension and a low FRC drive a tendency to atelectasis, which is exactly why CPAP and surfactant are effective.
Gas exchange depends on ventilation-perfusion (V/Q) matching and diffusion across the thin air-blood barrier.
Fetal haemoglobin (HbF) binds 2,3-BPG poorly, giving it a higher oxygen affinity and a left-shifted dissociation curve (lower P₅₀). This is ideal for taking up oxygen across the placenta, and is gradually replaced by adult HbA over the first months.
The conditions where this development and physiology play out: